It is reported that the adult mammalian central nervous system (CNS) shows little spontaneous regeneration after injury despite that fact that there are many molecules present which promote nerve and axonal growth. In contrast to the CNS, the adult peripheral nervous system (PNS) is capable of regenerating to some extent.
It is believed that the lack of regeneration in the CNS is caused by the presence of molecules which actively prevent or inhibit regeneration. Such molecules include Nogo (an antigen of the IN-1 antibody), myelin-associated glycoprotein, and myelin-oligodendrocyte glycoprotein.
Arginase is an enzyme that catalyzes the conversion of the amino acid arginine to urea and ornithine. Arginase has been reported to reverse the inhibition of neural regeneration in the central and peripheral nervous system. Thus, enhancing arginase activity would be beneficial for reversing the inhibition of neural regeneration.
Arginase I is a 35- to 38-kDa cytoplasmic protein that cleaves arginine into urea and ornithine. Arginine is the only substrate capable of donating the guanidine group necessary for nitric oxide production. Nitric oxide is produced from arginine by three nitric oxide synthase (NOS) isoforms. Nitric oxide production can be regulated by modulating the levels of arginine. Arginase I can limit the pool of arginine available for nitric oxide synthase (NOS), thereby influencing the production of nitric oxide.
Neuronal damage can be caused by excess levels of nitric oxide (NO). NO is a diffusible neuronal second messenger synthesized in the nervous system by three enzymes: neuronal NO synthase, endothelial NO synthase, and inducible NO synthase. Excess NO generated by NO synthase is associated with various neurodegenerative diseases and conditions, such as multiple sclerosis, dementia, Huntington's disease, Alzheimer's disease, etc.
The amino acid arginine is the only endogenous substrate of NO synthase. It is reported that arginase can reduce cell death in the nervous system by competing with NO synthase for their common substrate, arginine.
Therefore, enhancing arginase activity would be beneficial for promoting neural regeneration or reducing neural damage in diseases and conditions associated with neural damage.